How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome

Am J Med Genet A. 2018 Jan;176(1):151-155. doi: 10.1002/ajmg.a.38515. Epub 2017 Nov 12.

Abstract

A congenital myasthenia was suspected in two unrelated children with very similar phenotypes including several episodes of severe dyspnea. Both children had a 10q11.2 deletion revealed by Single Nucleotide Polymorphisms array or by Next Generation Sequencing analysis. The deletion was inherited from the healthy mother in the first case. These deletions unmasked a recessive mutation at the same locus in both cases, but in two different genes: CHAT and SLC18A3.

Keywords: choline acetyl-transferase; compound heterozygoty; single nucleotide polymorphisms array; vesicular acetyl-choline transporter.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence
  • Choline O-Acetyltransferase / genetics*
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 10*
  • Female
  • Genes, Recessive*
  • Genetic Association Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Mutation*
  • Myasthenic Syndromes, Congenital / diagnosis*
  • Myasthenic Syndromes, Congenital / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Phenotype*
  • Polymorphism, Single Nucleotide
  • Vesicular Acetylcholine Transport Proteins / genetics*

Substances

  • SLC18A3 protein, human
  • Vesicular Acetylcholine Transport Proteins
  • Choline O-Acetyltransferase